Outcomes of COVID-19 in patients with obinutuzumab compared with patients with rituximab: a retrospective cohort study.

BACKGROUND: Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. METHODS: We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. RESULTS: The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p < 0.001), and developed severe COVID-19 (33.3% vs. 4.7%, p < 0.001) were higher in patients with obinutuzumab than in those with rituximab. Multivariate analyses showed that obinuzumab treatment was associated with higher incidences of prolonged SARS-CoV-2 infection (OR 27.05, 95% CI 3.75-195.22, p = 0.001) and severe COVID-19(OR 15.07, 95% CI 2.58-91.72, p = 0.003). CONCLUSIONS: Our study suggested that patients treated with obinutuzumab had a higher risk of prolonged SARS-CoV-2 infection and severe COVID-19 than those treated with rituximab.

In Situ Vanadium Modification Induced a Back Interfacial Field Passivation Effect toward Efficient Kesterite Solar Cells beyond 11% Efficiency.

Realization of a high-quality back electrode interface (BEI) with suppressed recombination is crucial for Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. To achieve this goal, the construction of a traditional chemical passivation effect has been widely adopted and investigated. However, there is currently a lack of reports concerning the construction of a field passivation effect (FPE) for the BEI. Herein, considering the characteristic of the negligible difference in ionic radius between Mo (0.65 Å) and V (0.64 Å) as well as the presence of one less valence electron compared to Mo, vanadium (V) was employed and in situ incorporated into the MoSe2 interfacial layer during the deposition of the Mo:V electrode and selenization process. This allowed for the establishment of a desirable in situ VI-FPE interface with p-MoSe2:V/p-CZTSSe at the BEI. The p-type characteristic in MoSe2:V is attributed to the presence of the VMo acceptor; notably, the Fermi energy level of MoSe2:V has shifted downward by 0.62 eV compared to MoSe2, thereby facilitating the formation of an optimized band alignment between MoSe2:V and the absorber. Consequently, the photovoltaic parameters of the cell-FPE have experienced a significant increase due to the enhanced carrier transportation efficiency compared to cell-ref, resulting in a remarkable improvement in efficiency from 8.28 to 11.11%.

Quantitative assessment of choroidal parameters in type 1 macular neovascularization linked to central serous chorioretinopathy and neovascular age-related macular degeneration.

OBJECTIVE: To use ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) to evaluate the choroidal features of neovascular age-related macular degeneration (nAMD) and type 1 macular neovascularization (MNV) attributable to central serous chorioretinopathy (CSC). METHOD: A cross-sectional research was carried out to examine patients with type 1 MNV due to CSC (50 eyes) and nAMD (98 eyes) utilizing UWF SS-OCTA examinations. The scan procedure covered a vertical 20 mm × horizontal 24 mm region with 9 subfields. A typical set of 68 healthy eyes was used for comparison. The effects of different diagnoses on choroidal parameters were assessed using covariance tests, using gender and age as variables. RESULTS: The research showed that all choroidal characteristics were age-related (all p < 0.05). The calculated marginal averages of choroidal thickness (ChT) and choroidal volume (CV) in the central area were substantially lower in the nAMD group than in the CSC group and the normal group after age differences were taken into account (all p < 0.05). In both the superotemporal and temporal areas, the CSC group had a greater choroidal vascular index (CVI) compared to the nAMD group (p < 0.05). Additionally, the CSC group had a greater temporal area choriocapillaris density (CCD) than the nAMD group (p < 0.05). CONCLUSION: At the choroidal level, type 1 MNV due to CSC and nAMD may be distinguished by UWF SS-OCTA. Compared to the nAMD affected eyes, the CSC affected eyes had increased ChT, CV, CVI, and CCD in several areas. The two diseases could be distinguished based on ChT and CV.

A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling.

Prostate cancer bone metastasis is a predominant cause of death for prostate cancer (PCa) patients. However, the underlying mechanisms are poorly understood. Here, we report that high levels of RNF41 are associated with metastatic human prostate cancer. RNF41 silencing inhibits prostate cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that RNF41 induces K27- and K63-linked noncanonical polyubiquitination of MYO1C to enhance its stability and induce actin remodeling, which promotes PCa bone metastasis. RNF41 was significantly upregulated in metastatic prostate cancer tissues and positively associated with MYO1C expression. Furthermore, we show in intraarterial injected-bone metastasis xenograft model that targeting MYO1C stability by inhibition of RNF41 markedly suppressed PCa bone metastasis. Collectively, our findings identify RNF41 is an important regulator of prostate cancer cell growth and metastasis and targeting RNF41/MYO1C could be a valuable strategy to ameliorate prostate cancer progression and metastasis.

Machine Learning-based Nomograms for Predicting Clinical Stages of Initial Prostate Cancer: A Multicenter Retrospective Study.

OBJECTIVE: To construct and externally validate machine learning-based nomograms for predicting progression stages of initial prostate cancer (PCa) using biomarkers and clinicopathologic features. METHODS: Three hundred sixty-two inpatients diagnosed with PCa at the First Affiliated Hospital were randomly assigned to training and testing sets in a 3:7 ratio, while 136 PCa patients from People's Hospital formed the external validation set. Imaging and clinicopathologic information were collected. Optimal features distinguishing advanced prostate cancer (APC) and metastatic PCa (mPCa) were identified through logistic regression (LR). ML algorithms were employed to build and compare ML models. The best-performing algorithm established models for PCa progression stage. Models performance was evaluated using metrics, ROC curves, calibration, and decision curve analysis (DCA) in training, testing, and external validation sets. RESULTS: Following LR analyses, PSA (P = .001), maximum tumor diameter (P = .026), Gleason score (P <.001), and RNF41 (P <.001) were optimal features for predicting APC, while ALP (P <.001), PSA (P <.001), and GS score (P = .024) were for mPCa. Among ML models, the LR models exhibited superior performance. Consequently, the LR algorithm was used for the APC-risk-nomogram and mPCa-risk-nomogram construction, with AUC values of 0.848, 0.814, 0.810, and 0.940, 0.913, 0.910, in the training, testing, and external validation sets, respectively. Calibration and DCA curves affirmed nomograms' consistency and net benefits for clinical decision-making. CONCLUSION: In summary, ML-based APC-risk-nomogram and mPCa-risk-nomogram exhibit outstanding predictive performance for PCa progression stages. These nomograms can assist clinicians in finely categorizing newly diagnosed PCa patients, facilitating personalized treatment plans and prognosis assessment.

Efficacy and safety of efdamrofusp alfa versus aflibercept in participants with neovascular age-related macular degeneration: a randomized, double-masked, active-controlled, non-inferiority, phase 2 trial.

PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study PARTICIPANTS: A total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as -5 letters (80% CI). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Machine learning-based CT radiomics enhances bladder cancer staging predictions: A comparative study of clinical, radiomics, and combined models.

BACKGROUND: Predicting the accurate preoperative staging of bladder cancer (BLCA), which markedly affects treatment decisions and patient outcomes, using traditional clinical parameters is challenging. Nevertheless, emerging studies in radiomics, especially machine learning-based computed tomography (CT) image-based radiomics, hold promise in improving stage prediction accuracy in various tumors. However, the comparative performance and clinical utility of models for BLCA are under investigation. PURPOSE: We aimed to investigate the application value of machine learning-based CT radiomics in preoperative staging prediction by comparing the performance of clinical, radiomics, and clinical-radiomics combined models. METHODS: A retrospective cohort of 105 patients with initial BLCA was randomized into training (70%) and testing (30%) cohorts. Radiomics features were extracted from CT images using the optimal feature filter, followed by the application of the least absolute shrinkage and selection operator algorithm for optimum feature selection. Furthermore, machine learning algorithms were used to establish a radiomics model within the training cohort. Independent risk factors for muscle-invasive BLCA (MIBC) obtained by multivariate logistic regression (LR) analysis were separately used to construct a clinical model. For a clinical-radiomics fusion model, radiomics features were combined with clinical parameters. Performance was evaluated based on receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and standard performance metrics. RESULTS: Patients exhibited a significantly higher age (p = 0.029), larger tumor size (p = 0.01), and an increased neutrophil-to-lymphocyte ratio (NLR; p = 0.045) in the MIBC group than in the NMIBC group. LR analysis revealed age (p = 0.026), tumor size (p = 0.007), and NLR (p = 0.019) as significant predictors for constructing the clinical model. In the testing cohort, the radiomics model, which used an Support Vector Machine classifier, achieved the highest area under the curve (AUC) value of 0.857. The clinical-radiomics model outperformed the remaining two models, with AUC values of 0.958 and 0.893 in the training and testing cohorts, respectively. DeLong's test indicated significant differences between the three models. Calibration curves showed good agreement, and DCA confirmed the superior clinical utility of the clinical-radiomics model. CONCLUSIONS: Machine learning-based CT radiomics combined with clinical parameters was a promising approach in staging BLCA accurately, which outperformed the individual models. Integrating radiomics features with clinical information holds the potential to improve personalized treatment planning and patient outcomes in BLCA.

Retrospective study of the clinical manifestations and efficacy of immunotherapy for patients with acquired hemophilia A.

OBJECTIVE: Raising awareness of acquired hemophilia A (AHA) and early diagnosis is critical to reduce the associated mortality rate. We aimed to characterize acquired hemophilia in Chinese patients and evaluate the effectiveness of immunotherapy. METHODS: The clinical characteristics, laboratory test data, therapeutic approaches, and outcomes of 20 patients with AHA who were admitted to Xi'an Central Hospital between January 2012 and December 2020 were retrospectively studied. RESULTS: Nine of the patients (45%) were treated by single glucocorticoid administration; three (15%) with cyclophosphamide (CP) in combination with a glucocorticoid; four individuals (20%) received a combination therapy of rituximab with CP and glucocorticoid or rituximab with CP, vincristine, and a glucocorticoid; three (15%) by injection of human immunoglobulin in combination with a glucocorticoid; and one (5%) with CP alone. Six patients (30%) achieved total remission and 11 (55%) partial remission (PR), but three (15%) did not enter remission, indicating an objective response rate of 85%. CONCLUSION: Combination therapy with rituximab or intravenous human immunoglobulin achieves superior results in some patients with AHA. Immunosuppression and the administration of coagulation factors can rapidly control the disease and are efficacious, but >50% of patients only achieved PR. These findings suggest that the complete elimination of inhibitors requires prolonged immunosuppression therapy.

Clinical Characteristics and Prognosis of Heart Failure with Preserved Ejection Fraction Across Diverse Ejection Fraction Ranges.

Background: Recent studies have indicated that heart failure (HF) with preserved ejection fraction (HFpEF) within different left ventricular ejection fraction (LVEF) ranges presents distinct morphological and pathophysiological characteristics, potentially leading to diverse prognoses. Methods: We included chronic HF patients hospitalized in the Department of Cardiology at Hebei General Hospital from January 2018 to June 2021. Patients were categorized into four groups based on LVEF: HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF, 41% ≤ LVEF ≤ 49%), low LVEF-HFpEF (50% ≤ LVEF ≤ 60%), and high LVEF-HFpEF (LVEF > 60%). Kaplan‒Meier curves were plotted to observe the occurrence rate of endpoint events (all-cause mortality and cardiovascular mortality) within a 2-year period. Cox proportional hazards regression models were employed to predict the risk factors for endpoint events. Sensitivity analyses were conducted using propensity score matching (PSM), and Fine-Gray tests were used to evaluate competitive risk. Results: A total of 483 chronic HF patients were ultimately included. Kaplan‒Meier curves indicated a lower risk of endpoint events in the high LVEF-HFpEF group than in the low LVEF-HFpEF group. After PSM, there were still statistically significant differences in endpoint events between the two groups (all-cause mortality p = 0.048, cardiovascular mortality p = 0.027). Body mass index (BMI), coronary artery disease, cerebrovascular disease, hyperlipidemia, hypoalbuminemia, and diuretic use were identified as independent risk factors for all-cause mortality in the low LVEF-HFpEF group (p < 0.05). Hyperlipidemia, the estimated glomerular filtration rate (eGFR), and ß -blocker use were independent risk factors for cardiovascular mortality (p < 0.05). In the high LVEF-HFpEF group, multivariate Cox regression analysis revealed that age, smoking history, hypoalbuminemia, and the eGFR were independent risk factors for all-cause mortality, while age, heart rate, blood potassium level, and the eGFR were independent risk factors for cardiovascular mortality (p < 0.05). After controlling for competitive risk, cardiovascular mortality risk remained higher in the low LVEF-HFpEF group than in the high LVEF-HFpEF group (Fine-Gray p < 0.01). Conclusions: Low LVEF-HFpEF and high LVEF-HFpEF represent two distinct phenotypes of HFpEF. Patients with high LVEF-HFpEF have lower risks of both all-cause mortality and cardiovascular mortality than those with low LVEF-HFpEF. The therapeutic reduction in blood volume may not be the best treatment option for patients with high LVEF-HFpEF.

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. Methods: This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30 × 109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600 mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50 × 109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50 × 109/L or ≥100 × 109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30 × 109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. Findings: From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n = 4), zuberitamab 100 mg (n = 10), 300 mg (n = 8) and 600 mg (n = 10) groups. The primary endpoint (PLT ≥50 × 109/L at week 8) was achieved by 40% of patients in the 100 mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50 × 109/L or ≥100 × 109/L or an increase twice more than baseline as well as ≥30 × 109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600 mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100 mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100 mg-600 mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600 mg group, but gradually recovered at week 20. Three patients (2 in 100 mg and 1 in 600 mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA + patients may have higher response rates. Interpretation: This study preliminarily confirmed that 100 mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. Funding: National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Quantitative assessment of choroidal parameters and retinal thickness in central serous chorioretinopathy using ultra-widefield swept-source optical coherence tomography: a cross-sectional study.

OBJECTIVE: In this study, we used ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA) to assess changes in retinal thickness (RT) and choroidal parameters in individuals who had received a diagnosis of central serous chorioretinopathy (CSC). METHODS: The study encompassed the evaluation of 59 eyes from 47 patients with a diagnosis of CSC, alongside 33 fellow eyes and 31 eyes from healthy individuals (controls). The parameters assessed included RT, choroidal thickness (CT), choriocapillaris density, vascular density of the large choroidal vessel layer, three-dimensional choroidal vascularity index (3D-CVI), choroidal vessel volume per unit area (mCVV/a), and choroidal stroma volume per unit area (mCSV/a). RESULTS: Metrics including mCVV/a, mCSV/a, 3D-CVI, CT, and RT exhibited significantly elevated values in the eyes affected by CSC compared to those of the control group across nine subfields. Moreover, a substantial number of the subfields in both CSC-affected and fellow eyes exhibited increased values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT when compared with the control group. Additionally, acute and chronic CSC subfields demonstrated significantly elevated values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT in comparison to healthy control eyes. Notably, specific subfields associated with complex and atypical forms of CSC revealed higher metrics compared to those of the control group. CONCLUSION: In conclusion, the UWF SS-OCTA proved to be a valuable tool for exploring the anatomical etiology and clinical classification and diagnosis of CSC.

The antioxidant effect of tetrahedral framework nucleic acid-based delivery of small activating RNA targeting DJ-1 on retinal oxidative stress injury.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ-1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ-1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs-DJ-1 saRNAs). In vitro studies show that tFNAs-DJ-1 saRNAs can efficiently transfer DJ-1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE-19s, and significantly increased their cellular DJ-1 level. Reactive oxygen species expression in H2O2-treated HUVECs and ARPE-19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs-DJ-1 saRNAs were delivered. Moreover, tFNAs-DJ-1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs-DJ-1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ-1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress-related retinal disorders.

The prognostic significance and clinical relevance of stem cell characteristic in bladder cancer.

Background: Bladder cancer (BLCA) is a common malignant tumor of urinary system and prognostic biomarkers are needed for better clinical decision-making and patient management. Cancer stem cells (CSCs) are involved in carcinogenesis, development, metastasis and recurrence of BLCA. This study explored the prognostic and predictive value of CSCs-related genes and laid the groundwork for precision treatment development in BLCA. Methods: The mRNA data and corresponding clinical information obtained from TCGA-BLCA cohort was used to discover biomarkers and develop CSCs-related prognostic model, which was further validated in GSE32548 and GSE32894 datasets. In addition, the association between CSCs-related risk score and therapeutic efficacy was analyzed to explore the potential predictive value of the prognostic model. Results: We identified four CSCs-related subtypes and 900 differentially expressed genes (DEGs) among subtypes. Then the CSCs-related prognostic model was built based on 16 CSCs-related DEGs with the most significant prognostic value. Patients in the low-risk group had better overall survival than those in high-risk group (P < 0.001; HR, 0.42; 95 %CI, 0.31-0.57). Multivariable Cox analysis in training and test sets confirmed the independence of CSCs-related risk score as a prognostic factor (P < 0.05). The difference of survival between two risk groups were probably due to the significantly varied immune microenvironment based on the analysis of infiltrated immune cells. Additionally, the risk score was significantly associated with chemotherapy sensitivity and the response to anti-PD-L1 therapy (P < 0.05) which suggested a potential predictive value of CSCs-related risk model. Conclusion: We established a risk classifier based on 16 CSCs-related genes for predicting survival in patients with BLCA. The CSCs-related risk model has both prognostic value and potential predictive value for therapeutic efficacy, which brings us closer to understanding the important role of CSCs in BLCA and may provide guidance for clinical treatment decision-making and patient management. The clinical utility of the CSCs-related risk classifier warrants further studies.

Improvement of Efficiency in Kesterite Solar Cells by Intentionally Inserting a Thin MoS2 Layer into the Back Interface.

A Mo(S,Se)2 interfacial layer is formed inevitably and uncontrollably between the Mo electrode and Cu2ZnSn(S,Se)4 (CZTSSe) absorber during the selenization process, which significantly influences the performance of CZTSSe solar cells. In this work, an ultrathin MoS2 layer is intentionally inserted into Mo/CZTSSe to reduce the recombination and thus optimize the interface quality. It is revealed that the absorber exhibits a continuous and compact morphology with bigger grains and remarkably without pinholes across the surface or cross-sectional regions after MoS2 modification. Benefitting from this, the shunt resistance (RSh) of the device increased evidently from ∼395 to ∼634 Ω·cm2, and simultaneously, the reverse saturation current density (J0) realized an effective depression. As a result, the power conversion efficiency (PCE) of the MoS2-modified device reaches 9.64% via the optimization of the thickness of the MoS2 layer, indicating performance improvements with respect to the MoS2-free case. Furthermore, the main contribution to the performance improvement is derived and analyzed in detail from the increased RSh, decreased J0, and diode ideality factor. Our results suggest that the Mo/CZTSSe interface quality and performance of CZTSSe solar cells can be modulated and improved by appropriately designing and optimizing the thickness of the inserted MoS2 layer.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

Resonance-Assisted Surface-Enhanced Raman Spectroscopy Amplification on Hierarchical Rose-Shaped MoS2/Au Nanocomposites.

Surface-enhanced Raman spectroscopy (SERS) has emerged as a highly sensitive trace detection technique in recent decades, yet its exceptional performance remains elusive in semiconductor materials due to the intricate and ambiguous nature of the SERS mechanism. Herein, we have synthesized MoS2 nanoflowers (NFs) decorated with Au nanoparticles (NPs) by hydrothermal and redox methods to explore the size-dependence SERS effect. This strategy enhances the interactions between the substrate and molecules, resulting in exceptional uniformity and reproducibility. Compared to the unadorned Au nanoparticles (NPs), the decoration of Au NPs induces an n-type effect on MoS2, resulting in a significant enhancement of the SERS effect. This augmentation empowers MoS2 to achieve a low limit of detection concentration of 2.1 × 10-9 M for crystal violet (CV) molecules and the enhancement factor (EF) is about 8.52 × 106. The time-stability for a duration of 20 days was carried out, revealing that the Raman intensity of CV on the MoS2/Au-6 substrate only exhibited a reduction of 24.36% after undergoing aging for 20 days. The proposed mechanism for SERS primarily stems from the synergistic interplay among the resonance of CV molecules, local surface plasma resonance (LSPR) of Au NPs, and the dual-step charge transfer enhancement. This research offers comprehensive insights into SERS enhancement and provides guidance for the molecular design of highly sensitive SERS systems.

Pharmacological Effects of Shikonin and Its Potential in Skin Repair: A Review.

Currently, skin injuries have a serious impact on people's lives and socio-economic stress. Shikonin, a naphthoquinone compound derived from the root of the traditional Chinese medicine Shikonin, has favorable biological activities such as anti-inflammatory, antibacterial, immunomodulatory, anticancer, and wound-healing-promoting pharmacological activities. It has been reported that Shikonin can be used for repairing skin diseases due to its wide range of pharmacological effects. Moreover, the antimicrobial activity of Shikonin can play a great role in food and can also reduce the number of pathogenic bacteria in food. This paper summarizes the research on the pharmacological effects of Shikonin in recent years, as well as research on the mechanism of action of Shikonin in the treatment of certain skin diseases, to provide certain theoretical references for the clinical application of Shikonin, and also to provides research ideas for the investigation of the mechanism of action of Shikonin in other skin diseases.

Safety and efficacy of intravitreal injection of conbercept for the treatment of patients with choroidal neovascularization secondary to pathological myopia: Results from the SHINY study.

PURPOSE: To evaluate the safety and efficacy of intravitreal injections of 0.5 mg conbercept in patients with choroidal neovascularization secondary to pathological myopia (pmCNV). METHODS: The 177 pmCNV patients were randomly assigned in a 3:1 ratio to receive conbercept or sham injection, respectively. The conbercept group receive conbercept intravitreal injections administered on a pro re nata (PRN) basis after 3 monthly loading doses. The sham group received three consecutive monthly sham injections and then one conbercept injection followed by PRN conbercept intravitreal injections. RESULTS: At month 3, the mean BCVA for the two groups were improved by 12.0 letters (conbercept group, from 54.05 letters to 66.05 letters) and 0.6 letters (sham group, from 49.77 letters to 50.33 letters), respectively (p < 0.001). The mean central retinal thickness (CRT) at month 3 in the two groups decreased 62.0 µm (conbercept group, from 348.90 µm to 286.18 µm) and 4.4 µm (sham group, from 347.86 µm to 343.47 µm) (p < 0.001). At month 9, the mean BCVA improved by 13.3 letters in the conbercept group and 11.3 letters in the sham group. The mean CRT decreased 73.6 µm in the conbercept group and 55.9 µm in the sham group (p < 0.001). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival haemorrhage and increased intraocular pressure. CONCLUSION: Intravitreal injections of 0.5 mg conbercept provided improvement in visual and anatomical outcomes in pmCNV patients with low rates of ocular and nonocular safety events.

Sn-doped ZnO for efficient and stable quantum dot light-emitting diodes via a microchannel synthesis strategy.

ZnO nanocrystals (NCs) are widely employed as an electron transport layer (ETL) in quantum-dot light-emitting diodes (QLEDs). However, the excessive electron mobility, abundant surface defects and poor reproducibility of ZnO NC synthesis are currently the primary restrictive factors influencing the development of QLEDs. In this study, we developed Sn(IV)-doped ZnO NCs as the ETL for constructing highly efficient and long lifetime QLEDs. The introduction of Sn can reduce the surface hydroxyl oxygen defects and alter the electron transport properties of NCs, and thus is beneficial for improving the efficiency of hole-electron recombination in the emitting layer. Meanwhile, a microchannel (MC) reactor is utilized to finely control the synthesis of Zn0.96Sn0.04O NCs, enabling us to achieve uniform size distribution and consistent production reproducibility. Using the Sn(IV)-doped ZnO NCs as the ETL has led to a remarkable enhancement of external quantum efficiency (EQE) for the fabricated red QLED, from 9.2% of the ZnO only device to 15.5% of the Zn0.96Sn0.04O device. Furthermore, the T70 (@1000 cd m-2) of the Zn0.96Sn0.04O device reached 78 h, which is 1.77-fold higher than that of the ZnO only device (44 h). The present work provides an alternative ETL for efficient and stable QLEDs.